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Back on the chain gang: polyphosphate modification of proteins 回到链式团伙:蛋白质的多磷酸修饰。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.tibs.2024.06.010

Polyphosphate (polyP) mediates a plethora of biological functions. Understanding the polyP-protein interactome will help clarify the mechanisms underpinning these functions. Recent studies demonstrating a strong but noncovalent modification of lysine and histidine repeat proteins by polyP have provided new insights into polyP-protein biochemistry with implications for research and therapeutics.

聚磷酸盐(polyP)介导了大量生物功能。了解 polyP 蛋白相互作用组将有助于阐明这些功能的作用机制。最近的研究表明,polyP 能对赖氨酸和组氨酸重复蛋白进行强力但非共价的修饰,这为我们了解 polyP 蛋白的生物化学提供了新的视角,对研究和治疗具有重要意义。
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引用次数: 0
IUBMB Emerging Leader Award and Africa Initiative 国际生物化学和分子生物学联合会(IUBMB)新兴领导人奖和非洲倡议。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.06.001
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引用次数: 0
Double-duty isomerases: a case study of isomerization-coupled enzymatic catalysis 双重职责异构酶:异构化耦合酶催化案例研究。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.04.007

Enzymes can usually be unambiguously assigned to one of seven classes specifying the basic chemistry of their catalyzed reactions. Less frequently, two or more reaction classes are catalyzed by a single enzyme within one active site. Two examples are an isomerohydrolase and an isomero-oxygenase that catalyze isomerization-coupled reactions crucial for production of vision-supporting 11-cis-retinoids. In these enzymes, isomerization is obligately paired and mechanistically intertwined with a second reaction class. A handful of other enzymes carrying out similarly coupled isomerization reactions have been described, some of which have been subjected to detailed structure–function analyses. Herein we review these rarefied enzymes, focusing on the mechanistic and structural basis of their reaction coupling with the goal of revealing catalytic commonalities.

通常可以将酶明确归入七类中的一类,具体说明其催化反应的基本化学性质。一种酶在一个活性位点上催化两种或多种反应类别的情况并不多见。异构化水解酶和异构化加氧酶就是两个例子,它们催化异构化耦合反应,对生产支持视力的 11-顺式类视黄醇至关重要。在这些酶中,异构化必须与第二类反应配对,并在机制上相互交织。其他一些进行类似耦合异构化反应的酶已被描述,其中一些已进行了详细的结构-功能分析。在此,我们回顾了这些罕见的酶,重点研究了它们反应耦合的机理和结构基础,目的是揭示催化的共性。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/S0968-0004(24)00167-1
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引用次数: 0
Ancestral ribonucleases back in motion for evolutionary-dynamics guided protein design 祖先核糖核酸酶重新启动,以进化动力学为指导设计蛋白质。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.06.005

The dynamics behavior of a protein is essential for its functionality. Here, Doucet et al. demonstrate how the evolutionary analysis of conformational pathways within a protein family serves to identify common core scaffolds that accommodate branch-specific functional regions controlled by flexibility switches, offering a model for evolutionary-dynamics based protein design.

蛋白质的动力学行为对其功能至关重要。在本文中,Doucet 等人展示了如何通过对蛋白质家族内构象途径的进化分析来确定共同的核心支架,从而容纳由灵活性开关控制的特定分支功能区,为基于进化动力学的蛋白质设计提供了一个模型。
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引用次数: 0
Programmed cell death: NINJ1 and mechanisms of plasma membrane rupture 程序性细胞死亡:NINJ1 和质膜破裂机制
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.05.007

Lytic cell death culminates in cell swelling and plasma membrane rupture (PMR). The cellular contents released, including proteins, metabolites, and nucleic acids, can act as danger signals and induce inflammation. During regulated cell death (RCD), lysis is actively initiated and can be preceded by an initial loss of membrane integrity caused by pore-forming proteins, allowing small molecules and cytokines to exit the cell. A recent seminal discovery showed that ninjurin1 (NINJ1) is the common executioner of PMR downstream of RCD, resulting in the release of large proinflammatory molecules and representing a novel target of cell death-associated lysis. We summarize recent developments in understanding membrane integrity and rupture of the plasma membrane with a focus on NINJ1.

溶解性细胞死亡最终导致细胞肿胀和质膜破裂(PMR)。释放出的细胞内容物(包括蛋白质、代谢物和核酸)可作为危险信号并诱发炎症。在调节性细胞死亡(RCD)过程中,细胞裂解是主动启动的,在此之前,孔形成蛋白会造成细胞膜完整性的初步丧失,从而使小分子和细胞因子得以排出细胞。最近的一项重大发现表明,ninjurin1(NINJ1)是 RCD 下游 PMR 的共同执行者,它导致释放大量促炎分子,是细胞死亡相关溶解的一个新靶点。我们总结了了解膜完整性和质膜破裂的最新进展,重点介绍了 NINJ1。
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引用次数: 0
Protein lipoylation: mitochondria, cuproptosis, and beyond 蛋白质脂酰化:线粒体、杯突症及其他。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.04.002

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

蛋白质脂酰化是一种关键的翻译后修饰(PTM),在线粒体功能中起着举足轻重的作用,也是通过铜中毒导致细胞死亡的关键因素。这种由铜驱动的新型细胞死亡途径是由过量的铜离子与脂酰化线粒体蛋白结合而激活的,从而破坏能量的产生并导致致命的蛋白聚集和细胞死亡。蛋白质脂酰化、细胞能量代谢和杯突变之间错综复杂的关系为调节细胞的基本功能提供了一条前景广阔的途径。这篇综述重点探讨了脂肪酰化的机制及其对细胞新陈代谢和杯突症的重大影响,强调了其中涉及的关键基因及其对人类疾病的影响。它为针对失调的细胞代谢进行治疗提供了宝贵的见解。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/S0968-0004(24)00170-1
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引用次数: 0
Use of the ‘double diamond’ design framework to nurture creativity in life sciences research 利用 "双钻石 "设计框架培养生命科学研究的创造力。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.04.008

Designers' work processes are shaped by a four-phase ‘discover, define, develop, and deliver’ model that alternates between divergent and convergent thinking. We suggest consideration of this conceptual scaffold in ‘design sprint’ workshops for graduate students in the life sciences and in design to promote creativity, interdisciplinary collaboration, and knowledge cocreation.

设计师的工作流程由 "发现、定义、开发和交付 "四个阶段的模式形成,在发散思维和聚合思维之间交替进行。我们建议在为生命科学和设计专业研究生举办的 "设计冲刺 "研讨会中考虑使用这一概念支架,以促进创造力、跨学科合作和知识共创。
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引用次数: 0
Sharing is caring: TMEM165 a Golgi calcium importer used by the lysosome 分享就是关爱TMEM165 溶酶体使用的高尔基体钙离子输入器
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.tibs.2024.05.006

Calcium is a crucial second messenger in the cell that is stored in organelles including lysosomes. Proteins that facilitate calcium entry to the lysosome were unknown. A recent report by Zajac et al. identified TMEM165 as a proton-activated calcium importer on the lysosome, thus discovering a key player in subcellular calcium homeostasis.

钙是细胞中至关重要的第二信使,它储存在包括溶酶体在内的细胞器中。促进钙进入溶酶体的蛋白质尚不清楚。Zajac 等人最近的一篇报告发现 TMEM165 是溶酶体上的质子激活钙离子输入器,从而发现了亚细胞钙平衡中的一个关键角色。
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引用次数: 0
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